The major objectives of this research project include determination of the chemical structure and physical-chemical properties of polypeptide hormones, correlation of structure with biologic and immunologic activity, and detailed investigation of factors regulating the synthesis, storage, and secretion of these hormones from normal and abnormal endocrine cells. The project was initiated with a detailed analysis of the polypeptide hormone human placental lactogen (HPL), a protein closely related to human pituitary growth hormone and prolactin. The earlier results have established the amino acid sequence of HPL, its marked homology with growth hormone and a correlation in the biologic and immunologic properties of the two molecules. Further developments include the characterization of derivatives produced by a number of chemical and enzymic methods and attempts to identify the specific somatotrophic and lactogenic sites in each molecule. The analysis will be extended to other related hormones and may provide the opportunity to identify specific sequences of amino acids that could be synthesized for useful physiologic and clinical purposes. Extension of the biochemical studies involves physiologic and pathophysiologic studies of the synthesis, storage and secretion of hormones by the placenta, pituitary gland and other endocrine tissues. The laboratory has dealt extensively with a model system, utilizing parathyroid hormone synthesis and secretion in an attempt to derive a basis for examining cellular control mechanisms. The endocrine glands provide unique model systems for the study of mammalian cell regulation since the synthesis and release of their products is under the exquisite control of small molecules, ions and peptides. The physiologic function of cells in vitro will be correlated with their function in vivo, with histologic aspects of function and with simulated computer models for feedback regulation.